President Obama’s nominee for FDA commissioner yesterday told an audience of researchers his agency is working to advance translational medicine while balancing its desire to promote innovation with its need to protect public health.
Robert M. Califf, M.D., now deputy FDA commissioner for medical products and tobacco, said one key vehicle for achieving these goals will be the revised “Common Rule” governing clinical trials his agency and 15 other federal agencies are working to develop. FDA and the other agencies—including its parent, the U.S. Department of Health and Human Services—are soliciting public comment through December 7 on their proposal for a revised Common Rule.
The revised Federal Policy for the Protection of Human Subjects, unveiled last month and available here, would extend regulation to all clinical trials regardless of funding source if performed at a U.S. institution receiving any federal support, and if the trial is not regulated by the FDA.
The revised Common Rule also calls for the agencies to strengthen informed consent requirements, develop “reasonable and appropriate safeguards” to protect identifiable private information and biospecimens; and base independent review board requirements more closely on the harm intended to be avoided.
“We’re calling for much more activated patients, and much more proactive involvement with a position of broad consent starting out as people engage with medical care that will make it easier for researchers, if they have the proper credentials and rules, to use data to help people get better and [enable] better healthcare delivery,” Dr. Califf said, addressing the 10th Annual International Symposium of The University of Pennsylvania’s Institute for Translational Medicine and Therapeutics. The two-day symposium concludes today.
Dr. Califf said the FDA was also working to advance translational medicine by helping professionals generate more and better evidence to base sounder decisions—while retaining the agency’s role as an independent evaluator of treatments and technologies. This change, he said, was being driven by the rise of systems biology, the growth of public-private partnerships, and the challenge of analyzing the deluge of genomic data.
One component of that work, Dr. Califf said, was working with researchers to clarify how to think about biomarkers and how to distinguish the appropriate use of biomarkers in product development as well as clinical practice.
The issue he said he was most fascinated with was time. While researchers were long forced to study patients in clinics or hospitals if they wanted data over a period of time, Dr. Califf said the spread of cellphones and growth of social media allows investigators to gather much more of that data more easily than was possible before.
“We are working hard with the community to develop a framework for biomarker evaluation so that we can get rid of the ones that don’t work, keep the ones that do work, but also understand exactly what use they are,” Dr. Califf said. “Some biomarkers are great for predicting outcomes but terrible for assessing whether a treatment is effective, for example, there’s a lot of work to do to understand it. It takes the whole community to work together to do that. We’re doing this now with the science changing rapidly as it is in progress.”
Another component, he said, was improving how researchers gather and evaluate evidence.
Dr. Califf recalled a visit to the Multiple Myeloma Research Foundation two weeks ago. The foundation has helped develop new drugs that have shown success against the disease, and Dr. Califf said the foundation should be a model for other efforts to strengthen evidence gathering in ways that go beyond working on new treatments.
“They have a quality system and a way of having a database with biosamples and encouraging people with the illness to participate in clinical trials. We need this for every area of medicine, and we should all be working on it,” Dr. Califf said. “I think the tipping point is almost here,” he added, before acknowledging: “Right now, we’re not there. We’re delivering a fraction of what we need to deliver in terms of the evidence.”
“The name of the game is coming up with the best study, the best questions, and the best analytical methods. I really think we’re getting dangerously close to being able to do this, and it will reduce the cost considerably,” he added.
Dr. Califf offered several caveats for researchers in generating evidence. Researchers will need to embed randomized data into electronic health records while getting back to the basics of human phenotyping. Researchers will also have to accommodate greater patient participation in trials by increasingly knowledgeable patients.
Researchers and the FDA, he said, will need to work together in encourages patients to move beyond the images of advertising to truly understand the risks and benefits of their treatments.
As he had in a July address, Dr. Califf told researchers yesterday the FDA remained committed to carrying out its portion of President Obama’s initiative. That will include working with the NIH and the research community to develop a new approach to evaluating next-generation sequencing tests—because different tests often generate different analyses of genomic data—as well as developing a “data commons” where developers would furnish data demonstrating their tests’ characteristics.
“Let people compete based on the technology, but let’s, in a public way, identify the operating characteristics of the test, assure people that when they get a test, that it is accurate. And then the FDA’s job becomes relatively easy, because we can validate platforms,” Dr. Califf said.
Dr. Califf joined the FDA in February after 33 years with Duke University School of Medicine and the Duke University Medical Center—most notably vice chancellor of clinical and translational research and, in 2006, founder of the Duke University Clinical Research Institute.
Obama nominated Dr. Califf last month to succeed Margaret A. Hamburg, M.D., as FDA commissioner. While the U.S. Senate has been expected to confirm the nomination, Sen. Bernie Sanders (I-VT) on Friday said he would oppose Dr. Califf after concluding the nominee would not do enough to contain drug prices.
Sanders’ stance comes more than two weeks after his chief rival for the democratic presidential nomination, Hillary Rodham Clinton, unveiled a series of proposals aimed at cutting drug prices. Clinton has sought to capitalize on the furor over Turing Pharmaceuticals and its CEO Martin Shkreli raising the price of toxoplasmosis drug Daraprim from $13.50 to $750 a pill, then defending the 5,000% hike.
The controversy has touched off a sell-off in biotech stock by investors, and a fall in the prices of exchange traded funds specializing in biopharma shares.
Dr. Califf appeared to survive another potential challenge to his nomination that arose following the disclosure that he had his name removed as co-author of a series of articles published this month in the journal Clinical Trials. Some of those articles proposed reforms to FDA policies on clinical trial design that differ from those the agency’s policies—in one instance, suggesting that some patients need not provide informed consent for some trials.